Contrave is an anti-obesity drug that combines naltrexone and bupropion. The document provides an overview of Contrave and compares it to other FDA-approved anti-obesity medications. It summarizes results from four clinical trials of Contrave, which showed average weight losses of 5-9% compared to 1-2% for placebo after 1 year of treatment. The document also reviews Contrave's mechanism of action, dosing, and side effect profile. It concludes that Contrave provides effective long-term weight management and compares its efficacy and safety profile to other anti-obesity medications.

1. AN OVERVEW OF OBESITY and
ANTIOBESITY MEDICATIONS WITH AN
EMPHASIS ON CONTRAVE
Nicole Dean, Linh Huynh, and Dhara Shah
PharmD candidates 2016, MCPHS University
February 9,2016

2. OBJECTIVES
Identify risk factors and etiology of
obesity
Analyze different pharmacological
therapies for weight management
Compare CONTRAVE with other FDA-
approved anti-obesity drugs

3. INTRODUCTION
⦿ Obesity is a chronic disease associated with excess body
fat.
⦿ Obesity is the leading cause of mortality, morbidity,
disability, healthcare utilization, and healthcare costs in
the United States.
⦿ Obesity is a major risk factor for the top five diseases:
cardiovascular disease, cancer, stroke, and type 2
diabetes.
⦿ In total about 68.8% of Americans are obese or
overweight.
Please reference at bottom of
slide….each bullet should be
referenced unless these bullets were
derived from 1 source

4. WHO’S OBESE?
1. Obesity Prevalence Maps. (2015). Retrieved January 28, 2016, from http://www.cdc.gov/obesity/data/prevalence-
maps.html

5. WHO’S OBESE?
 The Midwest had the highest prevalence of obesity (30.7%), followed by the South
(30.6%), the Northeast (27.3%), and the West (25.7%) 1
1. Obesity Prevalence Maps. (2015). Retrieved January 28, 2016, from http://www.cdc.gov/obesity/data/prevalence-
maps.html

6. DOLLARS AND CENTS
⦿In 1998 cost of obesity was 78.5 billion
⦿Medicare and Medicaid paying for half of this cost who
pays the other half? Would be prepared to respond
⦿Due to current trends, the cost of obesity costs 40 billion
dollars more every four years. Indent after the last bullet
⦿ In 2008 the total cost of obesity increased to 147 billion.
Would make this bullet #2
⦿Annually 7 Billion dollars is spent on medications for
complications associated with obesity. Bullet #3
Disability and Obesity. (2015). Retrieved February 05, 2016, from
http://www.cdc.gov/ncbddd/disabilityandhealth/obesity.html

7. OBESITY RISK FACTORS
 Inadequate Diet / Physical
Activity
 Genetics / Family History
can play a minimum role if
developing the disease.
 Medication conditions can
lead to weight gain.
 Stress, diabetes,
Crushing’s syndrome,
hypothyroidism,
Polycystic ovary
syndrome (PCOS)
 Drugs leading to weight
gain
Insulin
Corticosteroids
Atypicals Antipsychotics
 Olanzapine
 Clozapine
Tricyclic Antidepressants
Can Prescription Drugs Cause Weight Gain? (n.d.). Retrieved February 05, 2016, from http://www.drugs.com/article/weight-gain.html
9 medical reasons for putting on weight. (n.d.). Retrieved February 05, 2016, from http://www.nhs.uk/Livewell/loseweight/Pages/medical-reasons-for-putting-on-
weight.aspx

8. PHARMACOLOGY OF
CONTRAVE AND OTHER
AVAILABLE ANTIOBESITY
DRUGS

9. Obesity Physiology

10. Pharmacological Weight Loss
Options
Tenuate® Xenical®
Alli®
(OTC)
Belviq® Qsymia® Saxenda® Contrave
®
Generic Diethyl-
propion
Orlistat Locaserin Phentermine
&
Topiramate
Liraglutide Naltrexone
&
Bupropion
Class Central
Nervous
Stimulant
Lipase
inhibitor
Serotonin
(5HT2c)
Receptor
Agonist
Sympatho-
mimetic &
Anti-
convulsant
Glucagon-
Like Peptide
(GPL-1)
Receptor
Agonist
Dopamine/
Norepi-
nephrine
Reuptake
Inhibitor &
Opioid
Antagonist
Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 01/27/16; accessed 01/27/16]

11. Neuropeptides Influence Appetite by exerting
their effects within the Hypothalamus
 What peptides suppresses appetite?
 Leptin, Insulin, GPL-1, PPY, MSH, Melanocortins, CRH,
CCK
 What peptides stimulates appetite?
 Ghrelin, NPY, AgRP, Opiods (especially μ), Galanin
 Which of these drugs is a GPL-1 aagonist, Teunate,
Xenical, Belviq, Qsymia, Saxenda, Contrave?
 Saxenda

12. Neurotransmitters Influence Appetite by
exerting their effects within the Hypothalamus
 What neurotransmitters suppresses appetite?
 Norepinephrine α1 β2
 Serotonin 5-HT1B and 5-HT2C
 Histamine H1 and H3
 Which serotonin subtype suppresses appetite?
 Norepinephrine α2 , Serotonin 5-HT1A

13. Neurotransmitters Influence Appetite by
exerting their effects within the Hypothalamus
 Which of these drugs can stimulate the NE receptor,
Teunate, Xenical, Belviq,Qysmia, Saxenda, Contrave?
 Tenuate, Qymia, Contrave
 Which of these drugs can stimulate the 5-HT2C
receptor, Teunate, Xenical, Qsymia, Belviq, Saxenda,
Contrave?
 Belviq

14. Enzymes Influence Appetite by exerting their
affects within the Gastrointestinal
 What is the function of the lipase?
 Hydrolyzes dietary triglycerides into absorbable fatty
acids
 Which of these drugs inhibits lipase, Teunate, Xenical,
Belviq, Saxenda, Qsymia, Contrave?
 Tenuate

15. Mechanism Of Action
Belviq, Qsymia,Saxenda,Xenical, and Contrave
Amazonaws.com. 2016. Available at: https://s3.amazonaws.com/classconnection/984/flashcards/5918984/png/screen_shot_2015-04-11_at_10447_pm-
14CA9DF33612FB6208F.png. Accessed January 29, 2016.

16. RECOMMENDED DOSING FOR OBESITY TREATMENT
Adapted from National Diabetes Education Initiative. Available online at:
http://www.ndei.org/dsl/searchslide.aspx?Slideid=3835&keyword=
Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. J Clin
Endocrinol Metab. 2015.100(2):342–362.

17. QUIZ TIME!
 WHAT ANTI-OBESITY AGENT IS AVAILABLE OTC?
A. CONTRAVE
B. XENICAL
C. ALLI
D. BELVIQ

18. A LITTLE MORE ABOUT CONTRAVE…

19. Contrave
Mechanism of Action
Christou G, Kiortsis D. The efficacy and safety of the naltrexone/bupropion combination for the treatment of obesity: an update. HJ. 2015.
doi:10.14310/horm.2002.1600.

20. Adapted from https://dailymed.nlm.nih.gov/dailymed/image.cfm?id=138957&name=image-01%2Ejpg
CONTRAVE STARTER PACKAGE

21. Adapted from Medscape.com: http://img.medscape.com/news/2014/ht_140916_contrave_800x600.jpg
CONTRAVE CONTENT PACKAGE

22. Adapted from drugs.com: http://www.drugs.com/imprints/nb-890-22385.html
HOW CONTRAVE PILLS LOOK LIKE:
CONTRAVE Appearance

23. Adapted from contrave.com: https://www.contrave.com/Images/pound-chart-2.png
WEIGHT REDUCTION WITH CONTRAVE
People taking Contrave
along with diet and exercise
counseling
People using diet and
exercise counseling
along
RESULTS - Lost 12lbs
(on average at 56 weeks with
initial average weight of 220lbs)
- Lost 3 lbs
(on average at 56 weeks
with initial average weight
of 219lbs)

24. CONTRAVE TRIALS

25. TITLES IINTERVENTION PRIMARY OUTCOME
MEASURES
RESULTS LIMITATION
A Multicenter, Randomized, Double
Blind, Placebo Controlled Study
Comparing the Safety and Efficacy of
Two Doses of Naltrexone Sustained
Release (SR)/Bupropion Sustained
Release (SR) and Placebo in Obese
Subjects (COR-I)
- 16mg-360mg/day
(NB16)
- 32mg-360mg/day
(NB32)
- Placebo
- Mean percent change
in body weight after 56
weeks (~ 1 year) from
baseline
- Proportion of subjects
≥5% decrease in body
weight from baseline
- NB16: -5%
NB32: -6.14%
Placebo: -1.33%
- NB16: 39.49%
NB32: 47.98%
Placebo: 16.44%
- subjects were generally
healthy middle-aged white
women with completion rate of
50% in all groups
- excluded individuals with
diabetes or active
cardiovascular disease
- only compared with placebo
(in all 4 studies)
A Multicenter, Randomized, Double
Blind, Placebo Controlled Study
Comparing the Safety and Efficacy of
Naltrexone Sustained Release
(SR)/Bupropion Sustained Release
(SR) and Placebo in Subjects with
Obese and Weight-related Risk
Factor (COR-II)
- NB32
- Placebo
- Mean percent change
in body weight after 28
weeks (~ 1 year) from
baseline
- Proportion of subjects
≥5% decrease in body
weight from baseline
- NB32: -6.45%
Placebo: -1.89%
- NB32: 55.64%
Placebo: 17.54%
- subjects were generally
healthy middle-aged white
women with completion rate of
54% in all groups
- individuals with diabetes were
excluded
- duration of study was only 28
weeks
A Multicenter, Randomized, Double
Blind, Placebo Controlled Study
Comparing the Safety and Efficacy
of Naltrexone 32 mg Sustained
Release (SR)/Bupropion 360 mg
Sustained Release (SR) and Placebo
in Obese Subjects With Type 2
Diabetes Mellitus (COR-Diabetes)
-NB32
-Placebo
- Mean percent change
in body weight after 56
weeks (~ 1 year) from
baseline
- Proportion of subjects
≥5% decrease in body
weight from baseline
- NB32: -5.03%
Placebo: -1.75%
- NB32: 44.53%
Placebo: 18.87%
- study excluded subjects who
were taking insulin therapy
(which can promote weight
gain) and GLP-1 (which is
asscoiated with mild weight
loss)
- relatively high drop-out rate
A Multicenter, Randomized,
Double-Blind, Placebo-Controlled
Study Comparing the Safety and
Efficacy of Naltrexone Sustained
Release (SR)/Bupropion SR and
Placebo in Subjects With Obesity
Participating in a Behavior
Modification Program (COR-
- NB32
- Placebo
- Mean percent change
in body weight after 56
weeks (~ 1 year) from
baseline
- Proportion of subjects
≥5% decrease in body
weight from baseline
- NB32: -9.02%
Placebo: -5.08%
- NB32: 66.39%
Placebo: 42.49%
- lack of male participants and
participants with significant
comorbidities

26. RECOMMENDATIONS and
COMPARISON

27. Adapted from National Diabetes Education Initiatives. Available at: http://www.ndei.org/dsl/searchslide.aspx?Slideid=3833&keyword=
Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. J Clin
Endocrinol Metab. 2015.100(2):342–362.
WHAT TO PICK??...

28. TENUATE XENICAL BELVIQ QSYMIA SAXENDA CONTRAVE
Long-term vs
short-term
Short-term
management
Long-term
management
Long-term
management
Long-term
management
Long-term
management
Long-term
management
Mean weight
loss
After 10
weeks, 14.8 lb
vs 9.0 lb of
placebo
After 4 years,
12.8 lb vs
6.6lb of
placebo 1
After 1 year, 12.8
lb (6%) vs 4.8 lb
(3%) of placebo
3
- 4.5% decrease
in weight in
T2DM 4
After 1 year,
17.8 lb (9%) in
7.5-46mg group
and 22.4lb (11%)
in 15-92mg
group
compared to
placebo (2%) 5
- Mean of 10.9%
weight loss also
seen in class II,
III obesity 6
After 2 years,
patients on 2.4
or 3mg had an
average weight
loss of 23.8 lb
(10.8 kg) 7
After 1 year,
(with
recommended
dosing of 32-
360mg/day),
6.14% weight
loss compared
to placebo
(1.33%)
- In patients
with T2DM,
5.03% weight
loss compared
to placebo
(1.75%),
Patient-
specific
For short-
term weight
loss up to 12
weeks
Patients who
usually have
fat-
containing
meals
At least one
weight-related
comorbidity*
and not
contraindicated
At least one
weight-related
comorbidity*
and not
contraindicated
At least one
weight-related
comorbidity*
and not
contraindicated
At least one
weight-related
comorbidity*
and not
contraindicated

29. TENUATE XENICAL BELVIQ QSYMIA SAXENDA CONTRAVE
Contraindication Arteriosclerosis
Substance abuse
Glaucoma
HTN
Hyperthyroidism
MAOI therapy
Cholestasis
Malabsorption
syndrome
N/A Glaucoma
Hyperthyroidism
MAOI therapy
Personal or
family history of
medullary
thyroid
carcinoma
Concomitant
use of
bupropion,
opiates or
alcohol
Uncontrolled
HTN
Seizure
disorders or past
history of
seizure
Pregnancy X X X X X X
Price (source:
Lexicomp)
25mg (100) -
$51.85
100mg (ER) (100)
- $130.17
Xenical 120mg
(90): $614.53
Alli 60mg (90):
$52.79
10mg (60):
$263.22
REMS
3.75-23 mg (30):
$216.12
7.5-46 mg (30):
$223.20
11.25-69 mg (30):
$239.40
15-92 mg (30):
$239.40
Injection:
18mg/3mL:
$236.59
8-90 mg (120):
$239.40
Insurance
Coverage
BC/BS = NC
Harvard Pilgrim
= NC
MassHealth = NC
BC/BS = PA
Harvard = NC
MassHealth =
NC
BC/BS = PA
Harvard =
NC
MassHealth
= NC
BC/BS = NC
Harvard = NC
MassHealth = NC
BC/BS = PA
Harvard = NC
MassHealth =
NC
BC/BS = PA
Harvard = NC
MassHealth =
NC

30. QUIZ TIME!
 NOT ALL MEDICATIONS REQUIRE A DIET PLAN !
TRUE
FALSE

31. QUIZ TIME!
 CONTRAVE HAS BEEN SHOWN TO BE SUPERIOR
THAN OTHER ANTI-OBESITY MEDICATIONS !
TRUE
FALSE

32. QUIZ TIME!
 IT IS USUALLY SAFE FOR OBESE PATIENTS, WHO
ARE ON ZYBAN FOR SMOKING CESSATION, TO
TAKE CONTRAVE.
TRUE
FALSE

33. Clinical Pearls of CONTRAVE
“Powerful drug not to be taken lightly” !!

35. REFERENCES
 Contrave. In: Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 01/27/16; accessed 01/27/16].
http://online.lexi.com.ezproxymcp.flo.org/lco/action/doc/retrieve/docid/patch_f/5338462
 Tenuate. In: Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 01/19/16; accessed 01/27/16].
http://online.lexi.com.ezproxymcp.flo.org/lco/action/doc/retrieve/docid/patch_f/6740
 Xenical. In: Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 01/27/16; accessed 01/27/16].
http://online.lexi.com.ezproxymcp.flo.org/lco/action/doc/retrieve/docid/patch_f/7402
 Belviq. In: Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 01/27/16; accessed 01/27/16].
http://online.lexi.com.ezproxymcp.flo.org/lco/action/doc/retrieve/docid/patch_f/3808862
 Qsymia. In: Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 01/19/16; accessed 01/27/16].
http://online.lexi.com.ezproxymcp.flo.org/lco/action/doc/retrieve/docid/patch_f/3832942
 Saxenda. In: Lexi-drugs Online. Hudson (OH): Lexi-Comp, Inc.;[updated 01/27/16; accessed 01/27/16].
http://online.lexi.com.ezproxymcp.flo.org/lco/action/doc/retrieve/docid/patch_f/2144379
 Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L. XENical in the prevention of diabetes in obese subjects
(XENDOS) study: A randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2
diabetes in obese patients. Diabetes Care 2004;27(1):155–161.
 Fidler MC, Sanchez M, Raether B, Weissman NJ, et al. A one-year randomized trial of lorcaserin for weight loss in
obese and overweight adults: The BLOSSOM trial. J Clin Endocrinol Metab 2011;96(10):3067–3077.
 O’Neil PM, Smith SR, Weissman NJ, et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss
in type 2 diabetes mellitus: The BLOOM-DM study. Obesity 2012;20(7):1426–1436.
 Gadde KM, Allison DB, Ryan DH, Peterson CA, et al. Effects of low-dose, controlled-release, phentermine plus
topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): A
randomized, placebo-controlled, phase 3 trial. Lancet 2011;377:1341–1352.
 Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: A
randomized controlled trial (EQUIP). Obesity 2012;20(2)330–342.
 Clements, J. N., & Shealy, K. M. (2015). Liraglutide An Injectable Option for the Management of Obesity. Annals of
Pharmacotherapy, 1060028015586806.

36. REFERENCES (cont)
 Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight loss in
overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3
trial. The Lancet. 2010;376(9741):595–605.
 Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight
and obesity-related risk factors (COR-II). Obesity. 2013;21(5):935–943.
 Hollander P, Gupta AK, Plodkowski R, et al. Effects of Naltrexone Sustained-Release/Bupropion Sustained-
Release Combination Therapy on Body Weight and Glycemic Parameters in Overweight and Obese Patients
With Type 2 Diabetes. Diabetes Care 2013;36:4022-4029. Diabetes Care. 2014;37(2):587–587.
 Wadden TA, Foreyt JP, Foster GD, et al. Weight Loss With Naltrexone SR/Bupropion SR Combination Therapy
as an Adjunct to Behavior Modification: The COR-BMOD Trial. Obesity. 2010;19(1):110–120.
 Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an Endocrine Society
clinical practice guideline. J Clin Endocrinol Metab. 2015.100(2):342–362.
 Obesity Prevalence Maps. (2015). Retrieved January 28, 2016, from
http://www.cdc.gov/obesity/data/prevalence-maps.html
 Christou G, Kiortsis D. The efficacy and safety of the naltrexone/bupropion combination for the
treatment of obesity: an update. HJ. 2015. doi:10.14310/horm.2002.1600.
 Sumnerdietrx.com. 2016. Available at: http://www.sumnerdietrx.com/files/2014/12/Contrave-
Ad_Portfolio-2014.png. Accessed January 29, 2016.
 Amazonaws.com. 2016. Available at:
https://s3.amazonaws.com/classconnection/984/flashcards/5918984/png/screen_shot_2015-04-
11_at_10447_pm-14CA9DF33612FB6208F.png. Accessed January 29, 2016.
 Google.com. bupropion pomc - Google Search. 2016. Available at:
https://www.google.com/search?q=bupropion+pomc&biw=1188&bih=563&source=lnms&tbm=isch&sa=
X&ved=0ahUKEwjMmMGY18_KAhUCPT4KHfuNBwcQ_AUIBigB#imgrc=H_juLQCeCoX6zM%3A.
Accessed January 29, 2016.
